Amino acids in CSF and plasma in hyperammonaemic coma due to arginase1 deficiency

We report the CSF and plasma amino acid concentrations and their ratios in a male patient with arginase1 deficiency with an unusual early presentation at 34 days of age. He developed hyperammonaemic coma (ammonia >400 μmol/L; normal <90 μmol/L) on postnatal day 35. CSF and plasma concentrations were assayed by ion-exchange chromatography on day 36. Arginine was increased both in plasma (971 μmol/L; controls (mean ± 2SD) 50 ± 42) and in CSF (157 μmol/L; controls 19 ± 8.6), resulting in a normal CSF/plasma ratio of 0.16 (controls 0.41 ± 0.26). Interestingly, glutamine was disproportionately high in CSF (3114 μmol/L; controls 470 ± 236) but normal in plasma (420 μmol/L; controls 627 ± 246); the ratio exceeded unity (7.4; controls 0.76 ± 0.31). The CSF/plasma ratios of most neutral amino acids were elevated but not those of the imino- and of the dibasic amino acids lysine and ornithine. The mechanism leading to the increase of most neutral amino acids in brain is not known.

A normal glutamine in plasma does not exclude an increased concentration in CSF; it could be useful to ascertain by MRS that a high CSF glutamine concentration truly reflects a high concentration in brain tissue for better understanding its pathogenesis.